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Neuman
Chapter 21
Chapter 21
Lipids
from
Organic Chemistry
by
Robert C. Neuman, Jr.
Professor of Chemistry, emeritus
University of California, Riverside
[email protected]
<http://web.chem.ucsb.edu/~neuman/orgchembyneuman/>
Chapter Outline of the Book
**************************************************************************************
I. Foundations
1.
Organic Molecules and Chemical Bonding
2.
Alkanes and Cycloalkanes
3.
Haloalkanes, Alcohols, Ethers, and Amines
4.
Stereochemistry
5.
Organic Spectrometry
II. Reactions, Mechanisms, Multiple Bonds
6.
Organic Reactions *(Not yet Posted)
7.
Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution
8.
Alkenes and Alkynes
9.
Formation of Alkenes and Alkynes. Elimination Reactions
10.
Alkenes and Alkynes. Addition Reactions
11.
Free Radical Addition and Substitution Reactions
III. Conjugation, Electronic Effects, Carbonyl Groups
12.
Conjugated and Aromatic Molecules
13.
Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids
14.
Substituent Effects
15.
Carbonyl Compounds. Esters, Amides, and Related Molecules
IV. Carbonyl and Pericyclic Reactions and Mechanisms
16.
Carbonyl Compounds. Addition and Substitution Reactions
17.
Oxidation and Reduction Reactions
18.
Reactions of Enolate Ions and Enols
19.
Cyclization and Pericyclic Reactions *(Not yet Posted)
V. Bioorganic Compounds
20.
Carbohydrates
21.
Lipids
22.
Peptides, Proteins, and α−Amino Acids
23.
Nucleic Acids
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*Note: Chapters marked with an (*) are not yet posted.
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Chapter 21
21: Lipids
Preview
21-2
21.1 Structures of Lipids
21-2
21-2
Fats, Oils, and Related Compounds (21.1A)
Fatty Acids.
A Comparison of Fats and Oils
Hydrogenation of Fats and Oils
Soaps
Detergents
Waxes
Glycerophospholipids
The Biological Origin of Fatty Acids
Prostaglandins (21.1B)
Terpenes and Steroids (21.1C)
Terpenes
Steroids
21.2 Biosynthesis of Lipids
Acetyl-CoA (21.2A)
Fatty Acids (21.2B)
Palmitic Acid
Types of Reactions in Palmitic Acid Biosynthesis
Other Fatty Acids
Fats, Oils and Phospholipids (21.2C)
Waxes (21.2D)
Prostaglandins (21.2E)
Terpenes (21.2F)
Steroids (21.2G)
Chapter Review
21-7
21-8
21-11
21-11
21-13
21-16
21-18
21-18
21-18
21-22
21-22
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Chapter 21
21: Lipids
•Structures of Lipids
•Biosynthesis of Lipids
Preview
Lipids are biological molecules soluble in organic solvents such as alcohols and ethers. They
include fats, oils, waxes, terpenes, steroids, prostaglandins, and molecular components of
membranes. We begin this chapter with an exploration of their structures and properties
and conclude it with a description of their biosynthetic origins. Lipids have different types
of functional groups so they are not a discrete "class" of organic molecules such as those we
have studied in previous chapters or will study in the final chapters of this text. However,
they share the common feature that their biosynthetic origin is the fundamental biological
building block acetyl CoA. [Figure 21.01]
Figure 21.01
21.1 Structures of Lipids
The functional groups of fats, oils, waxes, and prostaglandins are significantly different from
those of terpenes and steroids.
Fats, Oils, and Related Compounds (21.1A)
Fats and oils are triacylglycerols (triglycerides) with three ester (acyl) groups. [Figure
21.02]
Figure 21.02
These groups R1C(=O), R2C(=O), and R3C(=O) have unbranched carbon chains (typically
C12 to C24) that are saturated alkyl groups, or unsaturated groups with one or more C=C
double bonds. [Figure 21.03] [next page].
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Chapter 21
Figure 21.03
The three R groups can be the same (simple triglycerides) or different (mixed
triglycerides). We refer to triglycerides that are solid at room temperature as fats, and those
that are liquid as oils.
Fatty Acids. Hydrolysis of fats or oils converts their ester groups into free carboxylic
acids and glycerol. [Figure 21.04]
Figure 21.04
We call carboxylic acids from fats and oils fatty acids and common examples are given in
Table 21.1 [next page]. We will see later in the chapter that fatty acids have an even number
of C's because they form from CH3C(=O) groups in acetyl-CoA. The C=C bonds of
unsaturated fatty acids are cis.
A Comparison of Fats and Oils. Oils have higher percentages of unsaturated fatty acid
acyl groups, and lower percentages of saturated fatty acid acyl groups, than fats. You can
see this in the acyl group compositions of beef tallow (a fat) and peanut oil in Table 21.2
[next page]. The high percentage of unsaturated fatty acid acyl side chains in oils lowers their
melting points compared to fats of the same molecular mass because cis C=C bonds decrease
their solid-state packing efficiency.
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Chapter 21
Table 21.1. Some Common Fatty Acids
Cn
Structure
Saturated
C12
CH3-(CH2)10-CO2H
C14
CH3-(CH2)12-CO2H
C16
CH3-(CH2)14-CO2H
C18
CH3-(CH2)16-CO2H
Unsaturated*
C18
CH3-(CH2)7-(CH=CH-CH2)1-(CH2)6-CO2H
C18
CH3-(CH2)4-(CH=CH-CH2)2-(CH2)6-CO2H
C18
CH3-(CH2)1-(CH=CH-CH2)3-(CH2)6-CO2H
C20
CH3-(CH2)4-(CH=CH-CH2)4-(CH2)2-CO2H
Common Name
lauric acid
myristic acid
palmitic acid
stearic acid
oleic acid
linoleic acid
linolenic acid
arachidonic acid
* Structural formulas are abbreviated for ease of comparison.
Table 21.2. Comparative Acyl Group Composition of Beef Tallow and Peanut Oil
Acyl Group
Saturated
myristoyl (C14)
palmitoyl (C16)
stearoyl (C18)
(total %-saturated)
Unsaturated
oleoyl (C18)
linoleoyl (C18)
(total %-unsaturated)
Beef Tallow (a fat)
%-Acyl Group*
Peanut Oil (an oil)
%-Acyl Group*
4
30
20
(54)
0
10
4
(14)
40
2
(42)
45
30
(75)
*Total percentages are <100% because there are other acyl groups not listed.
Hydrogenation of Fats and Oils. Hydrogenation of fats or oils transforms unsaturated
acyl side chains into saturated acyl side chains as we show below for conversion of liquid
trioleoylglycerol (triolein, m.p. -5°) into solid tristearoylglycerol (tristearin, m.p. 55°).
Figure 21.05
Since oleoyl, linoleoyl, and linolenoyl groups are all C18, complete hydrogenation transforms
each of them into C18 stearoyl groups. Industrial laboratories use hydrogenation to increase
the melting points of fats and oils. You may have noticed that various "partially
hydrogenated" oils are ingredients in many food products. The major difference between
"soft margarines" sold in plastic tubs, and the harder margarine sold in wrapped "sticks" is
the extent of hydrogenation of the vegetable oils that are their primary ingredients.
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Partially Hydrogenated Vegetable Oils and Your Health. Nutritional experts tell us that highly
unsaturated triglycerides are better for our health than saturated triglycerides. Since hydrogenation
reduces unsaturation, we can conclude that partially hydrogenated fats and oils are less nutritionally
desirable than those that are not hydrogenated. During hydrogenation, cis C=C bonds isomerize to
trans C=C bonds and recent studies suggest that fats and oils with trans C=C bonds have the same
disadvantages with respect to our health as those with saturated side chains.
Soaps. Base catalyzed hydrolysis of fats or oils (saponification) gives sodium or
potassium salts of fatty acids that we call soaps [Figure 21.06].
Figure 21.06
Soaps are not lipids! We discuss them here because they come from lipids and are of
significant historical and commercial importance.
Early Soap Making. The art of making soap is thousands of years old. The Romans made soap by
heating animal fat with ashes from wood fires and early immigrants and pioneers in this country made
soap in the same way. Animal fat contains water, and ashes contain strong bases, so this soap-making
process is akin to saponification carried out in a laboratory.
Soaps work as cleansing agents in water because they combine with grease to form micelles.
Figure 21.07
These micelles are water miscible aggregates with polar (hydrophilic) exteriors and nonpolar
(hydrophobic) interiors. The long chain hydrocarbon "tails" of soap molecules dissolve in
grease droplets in water forming a micelle with the CO2- groups of the fatty acid carboxylates
on its surface. The negatively charged surface of the spherical micelle hydrogens bonds to
water molecules. This solubilizes grease so that the rinsing process removes it along with the
micelles.
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Detergents. While Na+ and K+ salts of fatty acid carboxylates (soaps) are soluble in
water, this is not the case for their Ca+2 and Mg+2 salts. Since hard water contains high
concentrations of Ca+2 and Mg+2 ions, the fatty acid carboxylate salts of these ions
precipitate when we add soaps to hard water. Beside being unsightly, this insoluble soap
"scum" ("bathtub ring") is not effective in solubilizing grease. In contrast, calcium and
magnesium salts of organic sulfonates (R-SO3-) with long alkyl chains (R) are water soluble.
Figure 21.08
Since these long chain organic sulfonates (synthetic detergents) form grease dissolving
micelles as effectively as soaps, they take the place of soaps in many cleaning products.
While soaps come from base catalyzed hydrolysis of natural fats and oils, most synthetic
detergents come from petroleum sources. Examples include Na+, or K+, or NR4 +
alkylbenzenesulfonates (R-Ph-SO3-) prepared by alkylation then sulfonation of benzene.
Figure 21.09
Waxes. Plants and animals synthesize high molecular mass esters called waxes.
Figure 21.10
The acyl components of waxes come from fatty acids that often have much higher molecular
masses than those of fats and oils. Their alcohol components arise from reduction of these
high mass fatty acids. Animal waxes include spermaceti from sperm whales, and beeswax.
A representative plant wax is Carnauba wax found on the leaves of Brazilian Wax Palms
(Table 21.3).
Table 21.3. Some Components of Animal and Plant Waxes.
Name
spermaceti
Formula
CH3-(CH2)14-C(=O)-O-CH2(CH2)14-CH3
beeswax
CH3-(CH2)14-C(=O)-O-CH2(CH2)28-CH3
CH3-(CH2)24-C(=O)-O-CH2(CH2)24-CH3
Carnauba wax
CH3-(CH2)30-C(=O)-O-CH2(CH2)30-CH3
CH3-(CH2)32-C(=O)-O-CH2(CH2)32-CH3
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Chapter 21
Naturally occurring "waxes" can be mixtures of different esters (waxes) and they can also
include small amounts of high molecular mass alkanes such as CH3(CH2)19CH3 and
CH3(CH2)27CH3 found in beeswax.
Glycerophospholipids. Biological membranes contain a number of different types of
molecular species including glycerophospholipids that we also call phosphoglycerides or
simply phospholipids. They are structurally similar to triglycerides except that they have an
organophosphate group as shown for phosphatidyl choline.
Figure 21.11
The Biological Origin of Fatty Acids. We have mentioned that fatty acids found as acyl
groups in fats, oils, and waxes, have an even number of C atoms because they form from C2
acyl groups of acetyl-CoA (CH3-C(=O)-SCoA). We will explore the reactions and
intermediates of these biosynthetic pathways later in this chapter.
Figure 21.12
Prostaglandins (21.1B)
Prostaglandins are C20 carboxylic acids containing a C5 ring substituted with a C8 chain, and
an adjacent C7 chain with a terminal CO2 H group.
Figure 21.13
Their common biosynthetic precursor is the C20 unsaturated fatty acid arachidonic acid
(four C=C bonds) that comes from linoleic acid (two C=C bonds) (see earlier Table 21.1 and
Figure 21.14)[next page]. Neither humans nor animals biosynthesize linoleic acid, so it is an
essential nutrient that we and they must obtain from sources such as plant fats and oils.
Prostaglandins such as those shown in Figure 21.15 [next page] have dramatic influences on
biological processes including inflammation, blood clotting, blood pressure, pain, fever, and
reproduction. We will outline their biosynthesis later in this chapter.
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Chapter 21
Figure 21.14
Figure 21.15
Terpenes and Steroids (21.1C)
Lipids that we have described so far all have ester or carboxylic acid functional groups and
even numbers of C atoms. None of these features characterize terpenes or steroids.
Terpenes. We find terpenes or derivatives of terpenes in both plants and animals. They
are branched polyenes with isolated C=C bonds, that often have no other functional groups.
Figure 21.16
We can dissect the carbon skeletons of terpenes into C5 fragments called isoprene units
(Figure 21.17) [next page]. You can think of an isoprene unit as a C2 "ethyl" fragment
bonded to the central C of a C3 "isopropyl" fragment. This "ethyl-isopropyl" skeleton is
called an isoprene unit because isoprene (2-methyl-1,3-butadiene) has the same C5 σskeleton.
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Chapter 21
Figure 21.17
We have highlighted isoprene units in some terpenes using structures that show just their
carbon σ-skeletons.
Figure 21.18
When you set out to identify isoprene units in a terpene, do not look for the conjugated C=C
bonds of isoprene. Most isoprene units in terpenes have only one C=C bond and its
position varies.
A consistent pattern for most terpenes is the "head" to "tail" attachment of isoprene units.
Figure 21.19
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Chapter 21
One of the terminal C's of the C3 fragment is its "head" (C1), while the terminal C of its C2
fragment is the end of its "tail" (C5). You can see in the structures in Figure 21.19 that C5
(the tail C) of one isoprene unit bonds to C1 (the head C) of another with the exception of
the central C5-C5 (tail to tail) bond in squalene.
While terpenes are structurally different from fats, oils, waxes, and prostaglandins, they are
lipids because of their solubility in organic solvents and their biosynthetic origin from acetylCoA described below.
Steroids. Steroids are lipids that arise from the terpene squalene. Squalene cyclizes in
three steps to give lanosterol that then gives cholesterol via a sequence of 19 reactions.
Figure 21.20
Cholesterol is the biosynthetic precursor of all steroid hormones (Figure 21.21)[next page].
While biochemists group steroids into five major categories as shown along with these
examples, they all have a number of common features. Each steroid has four fused rings
(three 6-membered rings and one 5-membered ring) labeled A, B, C, and D. They also have
an OH or keto group at C3, a methyl (or carbonyl) group at C10 and/or C13, and a side-chain
or OH group on C17.
When you consider the contrasting biological effects of testosterone and estradiol, it seems
amazing that there are such small differences in their chemical structures!
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Chapter 21
Figure 21.21
21.2 Biosynthesis of Lipids
We can include all lipids in a general biosynthetic scheme that begins with acetyl-CoA.
Figure 21.22
Acetyl-CoA (21.2A)
Acetyl-CoA is the product of reaction sequences in which carbohydrates (Chapter 20),
proteins (Chapter 22), and even fats and oils, break down via catabolic pathways.
Figure 21.23
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Chapter 21
Acetyl-CoA contains a C2 acetyl group (CH3-C(C=O)) bonded to a coenzyme called
Coenzyme A (CoA) and we show it at different levels of molecular detail in Figure 21.24.
Figure 21.24
CoA includes a nucleotide (adenosine-3'-phosphate) (Chapter 24), a pyrophosphate group,
and a large organic group ("R") containing two amide linkages and a terminal SH group. In
acetyl-CoA, the acetyl group replaces the H on the SH group of CoA (Figure 21.24).
We can represent acetyl-CoA as CH3-C(=O)-Y because its chemical reactivity is analogous to
that of carboxylic acid derivatives (R-C(=O)-Y) (Chapters 15 and 16). Nucleophiles can add
to the C=O group followed by loss of "Y-" or "YH" (overall nucleophilic substitution), and
bases can remove protons from CH3-C(=O) to give species that behave as enolate ions
(-CH2-C(=O)-Y). We will see such reactions in the following biosynthetic pathways and will
point out the analogies between them and those that we have studied in previous chapters.
Figure 21.25
Complete Details of the Biosynthetic Pathways. We will show only the most general features of
biosynthetic pathways in this chapter. We will not describe the structures of enzymes, or other
"biological reagents", that participate in these reactions. In some cases, we will depict transformations
as single steps when multiple steps actually occur. You will find many of these missing details in
modern biochemistry textbooks such as "Biochemistry", 2nd Edition, by D. Voet and J. G. Voet,
John Wiley & Sons, Inc., New York, N. Y., 1995.
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Chapter 21
Fatty Acids (21.2B)
Fatty acid biosynthesis occurs by several different pathways.
Palmitic Acid. One of these pathways combines eight C2 fragments from acetyl-CoA
(CH3-C(=O)-S-CoA) in a stepwise manner to give the C16 fatty acid palmitic acid.
Figure 21.26
It first transforms a C2 acetyl group (CH3C(=O)) into a C4 butryl group (CH3(CH2)2C(=O)),
then into a C6 hexanoyl group (CH3(CH2)4C(=O)), and so on in C2 increments until it
reaches the C16 palmitoyl group (CH3(CH2)14C(=O)).
In each of the 7 cycles of the pathway, the molecule that provides the C2 fragment to the
growing chain of the acyl group is not acetyl-CoA, but is one derived from its carboxylated
derivative malonyl-CoA (see Figure 21.27)[next page]. Before it provides the C2 fragment
to the growing acyl chain, the protein containing group ACP (acyl-carrier protein) replaces
the CoA group of malonyl-CoA. The resultant malonyl-ACP transfers the C2 fragment to the
growing acyl chain increasing its length from Cn to Cn+2.
ACP. If we represent the general structure of CoA as [nucleotide]-[pyrophosphate]-["R"], then we can
represent the general structure of ACP as [protein]-[phosphate]-["R"]. In CoA and ACP, the large
organic sequence ["R"] is the same and it binds to acyl groups via a terminal S atom (see Figure
21.24).
The growing acyl chain that receives the C2 fragment from malonyl-ACP in Step (3) is in bold
font in the general structure CH3-(CH2)n-C(=O)-S-ACP (an "acyl"-ACP) (Figure 21.27). In
the first reaction cycle, the "acyl"-ACP that reacts with malonyl-ACP in Step (3) is
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Figure 21.27
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Chapter 21
acetyl-ACP (CH3-C(=O)-S-ACP). It corresponds to the general "acyl"-ACP structure when
n = 0, and it forms directly from acetyl-CoA by a nucleophilic substitution of ACP for CoA.
In subsequent reaction cycles (Steps (3) through (6)), the "acyl"-ACP (CH3-(CH2)n-C(=O)S-ACP) that participates in Step (3) is the product of Step (6) of the preceding cycle. In the
final cycle, the "acyl"-ACP from Step (6) is palmitoyl-ACP (CH3-(CH2)14-C(=O)-S-ACP)
and it releases palmitic acid.
A Comment about these Formulas. The sulfur atom S attached to C=O is shown in structures such
as CH3-C(=O)-S-CoA or CH3-(CH2)n-C(=O)-S-ACP to emphasize that RC(=O)-Y is a thioester
(RC(=O)-S-R'). However, that S is actually part of CoA or ACP (see Figure 21.24). Although we
may not show S in general formulas such as acetyl-CoA that have no chemical symbols, it is still the
atom directly bonded to the acetyl group.
Types of Reactions in Palmitic Acid Biosynthesis. The reactions in Figure (Figure 21.27)
are analogous to reactions in previous chapters.
Step (1): Acetyl-CoA + CO2 → Malonyl-CoA
"Aldol-type" reaction involving nucleophilic addition of an enolate ion (-CH2C(=O)Y) to
carbon dioxide (O=C=O) (Chapter 18).
Step (2): Malonyl-CoA → Malonyl-ACP
Nucleophilic acyl substitution at C(=O)-Y (Chapter 16).
Step (3): Malonyl-ACP + "acyl"-ACP → β-ketoacyl-ACP + CO2
Malonic ester synthesis (Chapter 18).
Step (4): β-ketoacyl-ACP → β-hydroxyacyl-ACP
C=O reduction to an alcohol (Chapter 17).
Step (5): β-hydoxyacyl-ACP → α, β-unsaturated acyl-ACP
Dehydration of a β-hydroxycarbonyl compound (Chapter 18).
Step (6): α, β-unsaturated acyl-ACP → acyl-ACP
Hydrogenation of a C=C bond (Chapter 11).
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Chapter 21
Other Fatty Acids. Palmitic acid (C16) is the shortest fatty acid biosynthesized by
humans and higher animals. Elongase enzymes convert it into higher saturated fatty acids.
One elongase pathway uses the same sequence of steps as palmitic acid biosynthesis (Figure
21.27) except CoA rather than ACP binds to all acyl groups. Another elongase pathway also
uses CoA rather than ACP, but acetyl-CoA (rather than malonyl-CoA) provides the enolatetype ion in the chain-lengthening step (Step (3)). So Step (3) in this second elongase
pathway is a "Claisen-type" reaction (Chapter 18), not a "malonic ester-type" synthesis.
Desaturase enzymes dehydrogenate CH2CH2 groups in saturated or certain unsaturated
fatty acids to give cis CH=CH groups.
Figure 21.28
These "desaturase" reactions have specific restrictions on the values of "a" and "b" in the
structures shown in Figure 21.28, and on the positions of new C=C double bonds with
respect to existing C=C bonds. A major consequence is that many animals as well as humans
cannot biosynthesize linoleic acid (a crucial precursor of arachidonic acid and hence
prostaglandins). We and they must obtain it from external sources such as plant fats and oils
in order to sustain proper metabolism.
Fats, Oils and Phospholipids (21.2C)
The biosynthesis of fats, oils, and phospholipids requires not only fatty acids, but also the
glycerol portion of these glycerides.
Figure 21.29
This glycerol portion comes from fructose which organisms enzymatically convert to
dihydroxyacetone phosphate.
Figure 21.30
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Chapter 21
Dihydroxyacetone phosphate (or its C=O reduction product glycerol phosphate) reacts with
fatty acid acyl-CoA molecules to give triglycerides (fats and oils) or phospholipids.
Figure 21.31
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Chapter 21
The steps in which acyl-CoAs esterify OH groups are nucleophilic acyl substitutions at
C(=O)-Y groups (Chapter 16). The formation of dihydroxyacetone phosphate from fructose
diphosphate is a retro aldol reaction (Chapter 18).
Waxes (21.2D)
Biosynthesis of waxes occurs by esterification of fatty acids or fatty acid acyl groups with
long-chain alcohols (fatty alcohols).
Figure 21.32
Fatty alcohols come from reduction of fatty acids or fatty acid acyl groups. The alkanes
found along with esters in waxes, such as beeswax, have an odd number of C's and result from
decarboxylation of fatty acids (see Figure 21.32).
Prostaglandins (21.2E)
We mentioned earlier that prostaglandin formation in humans involves conversion of linoleic
acid to arachidonic acid followed by its transformation into prostaglandins (see Figure
21.14). Arachidonic acid arises from a pathway that uses desaturase and elongase enzymes
(Figure 21.33)[page 19]. Organisms store arachidonic acid as ester groups in phospholipids
and release it as needed for prostaglandin synthesis. Its conversion to prostaglandins
involves reactions with singlet O2 (see Chapter 11/17) catalyzed by enzymes (Figure
21.34)[page 19].
Terpenes (21.2F)
The C5 isoprene units in terpenes arise in a multistep biosynthetic pathway (Figure
21.35)[page 20]. (1) Three acetyl-CoA molecules condense via a "Claisen-type" reaction
followed by an "aldol-type" reaction to give the C6 compound β-hydroxy-βmethylglutaryl-CoA (HMG-CoA). (2) Reduction of the thioester group of HMG-CoA
gives the C6 compound mevalonic acid that is then converted to its pyrophosphate. (3)
Decarboxylation of phosphorylated mevalonate anion gives the C5 compound isopentenyl
pyrophosphate that serves as the source of the C5 isoprene units.
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Figure 21.33
Figure 21.34
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Figure 21.35
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Chapter 21
An example of terpene biosynthesis is that leading to the C30 terpene squalene.
Figure 21.36
squalene (C30)
Isopentenyl pyrophosphate combines with dimethylally pyrophosphate (formed by allyic
rearrangement of isopentenyl pyrophosphate) to give geranyl pyrophosphate (C10). It in
turn combines with another isopentenyl pyrophosphate to give farnesyl pyrophosphate.
Two farnesyl pyrophosphate molecules subsequently dimerize to give squalene.
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Chapter 21
The formation of geranyl or farnesyl pyrophosphate involves electrophilic addition of a
C+ (from ionization of a -C-O-P-P group) to the terminal C of the CH2 =C of isopentenyl
pyrophosphate.
Figure 21.37
In contrast, dimerization of farnesyl pyrophosphate occurs via formation of an intermediate
cyclopropane structure that subsequently opens to squalene via rearrangements of
carbocationic intermediates.
Figure 21.38
Steroids (21.2G)
Steroids have cholesterol as their common biosynthetic precursor (see Figure 21.21).
Cholesterol forms from squalene via the intermediate lanosterol (see Figure 21.20). The first
step of the three step biosynthesis of lanosterol is epoxidation of squalene. (Figure
21.39)[next page] A cascade of cycloaddition reactions leads to a carbocation that
subsequently rearranges and loses a proton to give lanosterol. The conversion of lanosterol
to cholesterol involves a 19-step sequence of reactions.
Chapter Review
Structures of Lipids
(1) Lipids include fats, oils, fatty acids, waxes, glycerophospholipids, prostaglandins, terpenes, and steroids.
They are biosynthesized from acetyl-CoA, generally soluble in organic solvents, but relatively insoluble in
water. (2) Fats, oils, and glycerophospholipids are esters of glycerol and long chain saturated or unsaturated
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Chapter 21
Figure 21.39
(cis C=C) carboxylic acids, with even numbers of C's, called fatty acids. (3) Waxes are esters of fatty acids and
fatty alcohols. (4) Soaps are fatty acid carboxylates, and detergents are long alkyl chain sulfonates, but they are
not lipids. (5) Prostaglandins, C20 carboxylic acids containing a C5 ring and two adjacent substituent chains,
are biosynthesized from the C20 unsaturated fatty acid arachidonic acid (4 C=C). (6) Terpenes contain C5
isoprene units with "head" to "tail" C-C bonds. (7) Steroids have a characteristic structure that is based on a
skeleton of four fused rings (A, B, C, D).
Biosynthesis of Lipids
(1) Acetyl-CoA (CH3 C(=O)-CoEnzyme A), the biosynthetic precursor of all lipids, forms by catabolism of
carbohydrates, or proteins, as well as fats and oils. (2) Palmitic acid (C16) arises from a repeated reaction
sequence involving stepwise carbonyl condensation reactions of C2 fragments originally from acetyl-CoA. (3)
Higher saturated and unsaturated fatty acids (including arachidonic acid) arise via reactions of existing fatty
acids with elongase and desaturase enzymes. (4) Fats, oils, and phospholipids originate from reactions of fatty
acid-CoA's and dihydroxyacetone phosphate formed from fructose. (5) Waxes arise by esterification of fatty acid
derivatives and fatty acid alcohols (reduction products of fatty acids). (6) Prostaglandins form via enzymatic
reactions of arachidonic acid with singlet oxygen. (7) Terpenes arise from electrophilic addition reactions of
dimethylallyl pyrophosphate (C5) and isopentenyl pyrophosphate (C5) from decarboxylation of mevalonic acid
(C6). Mevalonic acid comes from stepwise condensation reactions involving three acetyl-CoA's. (8)
Epoxidation of squalene followed by a series of cyclizations gives lanosterol that is subsequently transformed to
cholesterol, the precursor to steroid hormones.
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